FocusCancer Immunology

Tumor microenvironment on the move and the Aselli connection

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Science Signaling  28 Jun 2016:
Vol. 9, Issue 434, pp. fs13
DOI: 10.1126/scisignal.aag2279


  • Fig. 1 A common innate immune cell signaling mechanism orchestrates the reorganization of the TME and the response to microbial infection.

    Tumor cells (top) or normal epithelial cells (bottom) respond to independent stimuli to produce the sphingolipid S1P, among other factors. In a tumor, S1P is produced in response to ER stress or apoptosis caused by hypoxia, nutrient starvation, or the accumulation of lactic acid (LA) in the TME. In the gut or other epithelial barriers, S1P is produced in response to bacterial products, such as lipopolysaccharide (LPS) released by Gram-negative bacteria. In both contexts, S1P activates resident innate immunity myeloid cells (such as macrophages), leading to the transcriptional activation and secretion of LCN2, a siderophore-binding protein. Macrophage-secreted LCN2 promotes lymphangiogenesis (2), and LCN2 has been shown to promote EMT (5) and tumor growth through iron scavenging, which also limits bacterial growth. In their role to resolve inflammation, macrophages also release immunosuppressive cytokines, which enables tumor progression. Thus, conserved innate immune mechanisms—and specifically macrophages—are important in promoting cancer metastasis and limiting bacterial infection, two seemingly unrelated events. PI3K, phosphatidylinositol 3-kinase.


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